The present invention relates to processes for the preparation of spiroindolone compounds, such as (1′R,3′S)-5,7′-dichloro-6′-fluoro-3′-methyl-2′,3′,4′,9′-tetrahydrospiro[indoline-3,1′-pyrido[3,4-b]indol]-2-one.
(1′R, 3′S)-5,7′-dichloro-6′-fluoro-3′-methyl-2′,3′,4′,9′-tetrahydrospiro[indoline-3,1′-pyrido[3,4-b]indol]-2-one is useful in the treatment and/or prevention of infections such as those caused by Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, Trypanosoma cruzi and parasites of the Leishmania genus such as, for example, Leishmania donovani., and it has the following structure:

(1′R, 3′S)-5,7′-dichloro-6′-fluoro-3′-methyl-2′,3′,4′,9′-tetrahydrospiro[indoline-3,1′-pyrido[3,4-b]indol]-2-one and a synthesis thereof are described in WO 2009/132921 AI in particular in Example 49 therein.
There is a need to provide new process for the preparation of (1′R, 3′S)-5,7′-dichloro-6′-fluoro-3′-methyl-2′,3′,4′,9′-tetrahydrospiro[indoline-3,1′-pyrido[3,4-b]indol]-2-one in order to improve the overall efficiency of the synthesis to make it suitable for manufacturing. In particular, there is a need to increase the efficiency of synthesizing the chiral amine intermediate (IIA):
